Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide

Abstract Lumican is a small leucine-rich proteoglycan (SLRP) being known as a key regulator of collagen fibrillogenesis. However, little attention has been given so far in studying its influence on tumor-associated matrix architecture. Here, we investigate the role of host lumican on tumor matrix or...

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Autores principales:	Albin Jeanne, Valérie Untereiner, Corinne Perreau, Isabelle Proult, Cyril Gobinet, Camille Boulagnon-Rombi, Christine Terryn, Laurent Martiny, Stéphane Brézillon, Stéphane Dedieu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c046d2d73c534d8cab21461a5d461157
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spelling	oai:doaj.org-article:c046d2d73c534d8cab21461a5d4611572021-12-02T16:06:51ZLumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide10.1038/s41598-017-07043-92045-2322https://doaj.org/article/c046d2d73c534d8cab21461a5d4611572017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07043-9https://doaj.org/toc/2045-2322Abstract Lumican is a small leucine-rich proteoglycan (SLRP) being known as a key regulator of collagen fibrillogenesis. However, little attention has been given so far in studying its influence on tumor-associated matrix architecture. Here, we investigate the role of host lumican on tumor matrix organization as well as on disease progression considering an immunocompetent model of melanoma implanted in Lum −/− vs. wild type syngeneic mice. Conjointly, lumican impact on tumor response to matrix-targeted therapy was evaluated considering a previously validated peptide, namely TAX2, that targets matricellular thrombospondin-1. Analysis of available genomics and proteomics databases for melanoma first established a correlation between lumican expression and patient outcome. In the B16 melanoma allograft model, endogenous lumican inhibits tumor growth and modulates response to TAX2 peptide. Indeed, IHC analyses revealed that lumican deficiency impacts intratumoral distribution of matricellular proteins, growth factor and stromal cells. Besides, innovative imaging approaches helped demonstrating that lumican host expression drives biochemical heterogeneity of s.c. tumors, while modulating intratumoral collagen deposition as well as organization. Altogether, the results obtained present lumican as a strong endogenous inhibitor of tumor growth, while identifying for the first time this proteoglycan as a major driver of tumor matrix coherent assembly.Albin JeanneValérie UntereinerCorinne PerreauIsabelle ProultCyril GobinetCamille Boulagnon-RombiChristine TerrynLaurent MartinyStéphane BrézillonStéphane DedieuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Albin Jeanne Valérie Untereiner Corinne Perreau Isabelle Proult Cyril Gobinet Camille Boulagnon-Rombi Christine Terryn Laurent Martiny Stéphane Brézillon Stéphane Dedieu Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide
description	Abstract Lumican is a small leucine-rich proteoglycan (SLRP) being known as a key regulator of collagen fibrillogenesis. However, little attention has been given so far in studying its influence on tumor-associated matrix architecture. Here, we investigate the role of host lumican on tumor matrix organization as well as on disease progression considering an immunocompetent model of melanoma implanted in Lum −/− vs. wild type syngeneic mice. Conjointly, lumican impact on tumor response to matrix-targeted therapy was evaluated considering a previously validated peptide, namely TAX2, that targets matricellular thrombospondin-1. Analysis of available genomics and proteomics databases for melanoma first established a correlation between lumican expression and patient outcome. In the B16 melanoma allograft model, endogenous lumican inhibits tumor growth and modulates response to TAX2 peptide. Indeed, IHC analyses revealed that lumican deficiency impacts intratumoral distribution of matricellular proteins, growth factor and stromal cells. Besides, innovative imaging approaches helped demonstrating that lumican host expression drives biochemical heterogeneity of s.c. tumors, while modulating intratumoral collagen deposition as well as organization. Altogether, the results obtained present lumican as a strong endogenous inhibitor of tumor growth, while identifying for the first time this proteoglycan as a major driver of tumor matrix coherent assembly.
format	article
author	Albin Jeanne Valérie Untereiner Corinne Perreau Isabelle Proult Cyril Gobinet Camille Boulagnon-Rombi Christine Terryn Laurent Martiny Stéphane Brézillon Stéphane Dedieu
author_facet	Albin Jeanne Valérie Untereiner Corinne Perreau Isabelle Proult Cyril Gobinet Camille Boulagnon-Rombi Christine Terryn Laurent Martiny Stéphane Brézillon Stéphane Dedieu
author_sort	Albin Jeanne
title	Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide
title_short	Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide
title_full	Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide
title_fullStr	Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide
title_full_unstemmed	Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide
title_sort	lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted tax2 therapeutic peptide
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c046d2d73c534d8cab21461a5d461157
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Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide

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